MEDICINAL PLANTS AS MODULATORS OF THE GUT-BRAIN AXIS: A NARRATIVE REVIEW ON THEIR THERAPEUTIC IMPLICATIONS IN ANXIETY

Resumo

Anxiety significantly impacts quality of life and represents one of the leading causes of global disability. According to the World Health Organization, Brazil has one of the highest prevalences of anxiety disorders worldwide. Recent evidence highlights the role of chronic inflammation and dysregulation of the gut -brain axis in the pathophysiology of this condition. The bidirectional communication between the central nervous system (CNS), enteric nervo us system (ENS), and endocrine system, known as the “microbiota -gut-brain axis,” proposes the interaction of the intestinal microbiota with the nervous system, influencing physiological processes, cognition, and emotions through neural, immunological, and chemical signals. Herbal medicines, used since ancient times, contain active compounds with preventive and therapeutic potential, obtained from different parts of plants. In this context, the present study aims to develop a bibliographic review on the action of medicinal plants in modulating the gut -brain axis and their influence on anxiety. A narrative review was conducted, structured according to SANRA guidelines, using the PubMed database. The search was performed using the descriptors: “gut -brain axis,” “microbiota,” “phytotherapy,” “anxiety,” and “chronic inflammation,” combined with Boolean operators (AND/OR). Randomized clinical trials and systematic reviews published between 2021 and 2026 in English were included. Experimental animal studies, case re ports, and articles without full-text availability were excluded. Study selection was carried out through the screening of titles and abstracts, followed by full -text analysis of eligible articles. The findings indicate that medicinal plants may modulate t he microbiota -gut-brain axis through neurobiological and immunomodulatory effects. As an example, Crocus sativus L. (saffron) stands out, as it contains compounds with anti -inflammatory and antioxidant activity, including inhibition of the NLRP3 inflammasome and neutralization of superoxide anions. Its anxiolytic effects are associated with the inhibition of monoamine reuptake, agonist activity at GABAergic receptors, and antagonism of NMDA receptors. Withania somnifera (ashwagandha) has also been described , containing withanolides, alkaloids, and flavonoids associated with anxiolytic and immunomodulatory effects. Withaferin A acts mainly through the selective modulation of glucocorticoid receptors (GR), in addition to its anti- inflammatory activity. The potential anxiolytic effect involving the GABAergic system is more strongly attributed to the whole plant extract than to the isolated compound. Finally, Melissa officinalis contains triterpenes, phenolic acids, and flavonoids with anxiolytic, sedative, and neuroprotective effects, acting through the inhibition of GABA transaminase and monoamine oxidase-A (MAO-A), as well as by increasing serotonergic neurotransmission. Evidence suggests that the use of Crocus sativus L., Melissa officinalis L., and Withania somnifera exerts anxiolytic effects through the integrated modulation of neuroinflammatory pathways, neurotransmitter systems, and the microbiota-gut-brain axis. Additionally, evidence suggests that these species may influence the composition and metabolic activity of the intestinal microbiota, contributing to the regulation of inflammatory pathways and neurochemical signaling involved in anxiety; however, studies are predominantly focused on experimental models, with a scarcity of clinical data in humans. Furthermore, there is no consensus regarding the associated risks and benefits, highlighting the need for more robust and standardized clinical investigations to support the consolidation of their therapeutic use.